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The success of radiotherapy decisively depends on how sensitive the tumour is to radiation. Radiation sensitivity of tumour and normal tissue are the most important parameters radiotherapy must consider for optimal outcome. At the University Duisburg-Essen, so-called prompt double-strand breaks (prDSBs) have been identified as a surrogate predictor of cellular radiation sensitivity. The method enables the determination of radiosensitivity of each tumour, and possibly also of surrounding healthy, tissue, and can be used to generate individualized treatment plans.
Keywords: Strahlenempfindlichkeit, Tumor, Krebs, Induktion von DNA-Doppelstrangbrüchen, prädiktives Verfahren, Strahlentherapie, Bestrahlungsplanung, Surrogat-Prädiktor, Messung der DNA-Doppelstrangbrüche, Komet-Test, Einzelzellanalyse, Radiosensitivity, tumour, cancer, functional assay, induction of DNA double-strand breaks, predictive method, radiotherapy, irradiation planning, surrogate predictor, measurement of DNA double-strand breaks, comet assay, single cell analysis
The gold standard for determining radiation sensitivity (cell death as function of radiation dose) is the colony formation of single cells. However, the method can not be implement for routine use in the clinic, because it is too time-consuming and expensive (cell cultivation after irradiation takes 2-3 weeks). The same applies to an alternative approach, which addresses the repair of double-strand breaks (DSBs) as a surrogate predictor of cellular radiation sensitivity. Furthermore, the results are prone to be strongly affected by the physiological status of the cells due to cultivation, which is necessary for the determination.
The inventive method solely detects double-strand breaks induced promptly by radiation (prDSBs) and excludes DSBs developing subsequently due to the conversion to breaks of radiation induced heat labile lesions (tlDSBs). Since irradiated cells are analyzed immediately, determination of prDSBs induction is not affected by cell physiology. When using single cell assays, only a few hundred cells are required and results are available within 4 days.
- reliable correlation of prDSBs with cellular radiation sensitivity
- little sample material is required (via fine needle biopsy)
- results within a few days
- easy to handle test for use in the clinic (development planned, also in cooperation with interested parties)
The main potential lies in the clinical use for planning of radiation therapy administered to about half of the patients suffering from cancer. Furthermore, the method could be used in radiation protection and research. The technology is offered for licensing and further development as test.
Results for the determination of prDSBs are available for 15 tumor cell lines. The aim is to develop a clinical practicabel method that measures the induction exclusively of prDBSs via single cell analysis (comet assay). Subsequently, an automation of the determination would follow. In case of interest we are pleased to inform you about the patent status.
Cheng, Y. et al. (2015) The yield of DNA double strand breaks determined after exclusion of those forming from heat-labile lesions predicts tumor cell radiosensitivity to killing. Radiotherapy and Oncology. 116 (3): 366-373